Phosphonic acids and their derivatives have become increasingly important in recent years due to their useful biological properties, such as their ability to lower blood pressure due to their angiotensin converting enzyme inhibition activity, such as disclosed in U.S. Pat. No. 4,316,896 to Thorsett, et al. and U.S. Pat. Nos. 4,168,267 to Petrillo and 4,452,790 to Karanewsky, et al.
The Arbuzov reaction of trialkylphosphites with suitable alkylating agents is a commonly used method for the preparation of phosphonic acid esters but it often requires high temperatures, neat reaction mixtures and other strong impractical conditions. Additionally, complex product mixtures are common due to competitive alkylation by alkyl halide side products generated in the reaction.
Z. Pelchowicz, J. Chem. Soc. 1961, 238 discloses the preparation of phosphonic acid esters by base catalyzed alkylation or base catalyzed Michael addition each of which frequently requires strongly alkaline conditions.
M. Green and R. F. Hudson, J. Chem. Soc. 1958, 3129 disclose the free radical addition of dialkylphosphites and derviatives which usually requires high reaction temperatures and pressures, while only affording moderate to low yields and mixtures of products.
The oxidation of phosphonous acids or its esters to phosphonic acids or its esters often requires strong, poisonous, expensive and gaseous reagents, namely, mercuric salts, periodates, nitrogen oxide gases and the like. E. K. Baylis, C. D. Campbell and J. G. Dingwall, J. Chem. Soc. Perkin Trans. 1, 2845 (1984), G. M. Kosolapoff and L.Maier, "Organic Phosphonous Compounds, Wiley-Interscience, N.Y. 1972, Vol. 4, pages 288 and 294-295 and Vol. 7, page 11, R. N. Mehrotra, Can. J. Chem., 63, 663 (1985); C. F. Guichard, Chem. Bev., 32 1572 (1899).
The oxidation of triphenylmethyl, phosphonous acid and dibenzyl phosphonous acids to the corresponding phosphonic acids is mentioned by H.K. Hatt, J. Chem. Soc. 776 (193) and A. Michaels, Liebigs Ann. Chem., 315 51 (1901).
Thus, a mild efficient inexpensive method for preparing phosphonic acids which may be used in making phosphonyloxyacylamino acid angiotensin converting enzyme inhibitors would be a most welcomed addition to the art.